Heart Failure Phenotypes Induced by Knockdown of USMG5 in Zebrafish: A New Insight Into Mechanism of Dilated Cardiomyopathy

• Project/Area Number: 17K15995
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kanazawa University
• Principal Investigator: Nagata Yoji 金沢大学, 医学系, 協力研究員 (50632478)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 拡張型心筋症 / ミトコンドリア / 拡張側心筋症 / 心不全 / 分子生物学

Outline of Final Research Achievements

Heart failure was induced by inhibiting gene expression of z-usmg5(Up-regulated during skeletal muscle growth protein 5) in zebrafish which was a mitochondrial factor. Inhibition of USMG5 gene expression affected the expression of genes in conjunction with the apoptosis in the comprehensive gene analysis using a neonatal mouse cardiomyocyte. Furthermore, it demonstrated that USMG5 have relation to JNK phosphorylation in a pathway analysis.

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアは細胞内でエネルギーを産生する小器官であり、その異常により様々な疾患の原因となることが知られている。循環器疾患では、心不全状態にある心筋細胞においてミトコンドリア機能異常が認められており、今回我々は、ミトコンドリアに存在するUSMG5(Up-regulated during skeletal muscle growth protein 5)因子と心不全を呈する拡張型心筋症の関わりについて検討した。動物モデルで検討した結果、USMG5異常は、拡張型心筋症を誘発することが認められた。この結果から拡張型心筋症に対する新規治療の標的としてUSMG5が期待される。

Research Products

• [Journal Article] Impact of functionalstudies on exome sequence variant interpretation in early-onset cardiacconduction system diseases. (2020)
  • Author(s): Hayashi K, Teramoto R, Nomura A, Asano Y, Beerens M, Kurata Y, Kobayashi I, Furusho H, Onoue K, Chiang DY, Kiviniemi TO, Buys E, Sips P, Burch ML, Zhao Y, Kelly AE, Takeda Y,Konno T, Inoue M, Fujita T, Kato T, Tada H, Nagata Y, Cui S, Saito Y, MacRaeCA, Takashima S, Yamagishi M, Kawashiri MA, Takamura M. et al.
  • Journal Title: Cardiovasc Res. Volume: - Pages: -
  • DOI: 10.1093/cvr/cvaa010.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Functional analysis of KCNH2 gene mutations of type 2 long QT syndrome in larval zebrafish using microscopy and electrocardiography. (2019)
  • Author(s): Tanaka Y, Hayashi K, Fujino N, Konno T, Tada H, Nakanishi C, Hodatsu A, Tsuda T, Nagata Y, Teramoto R, Yoshida S, Nomura A, Kawashiri MA, Yamagishi M.
  • Journal Title: Heart Vessels. Volume: 34(1) Pages: 159-166
  • DOI: 10.1007/s00380-018-1231-4.
  • Peer Reviewed
• [Journal Article] Heart Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy. (2017)
  • Author(s): Nagata Y, Yamagishi M, Konno T, Nakanishi C, Asano Y, Ito S, Nakajima Y, Seguchi O, Fujino N, Kawashiri MA, Takashima S, Kitakaze M, Hayashi K.
  • Journal Title: Scientific Reports Volume: 7 Pages: 17417
  • DOI: 10.1038/s41598-017-17572-y
  • Peer Reviewed / Open Access
• [Presentation] DCM Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight from Mitochondriopathy (2018)
  • Author(s): Yoji Nagata
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] DAPIT Knockdown Induces Dilated Cardiomyopathy Phenotypes in Zebrafish (2017)
  • Author(s): Yoji Nagata
  • Organizer: AHA2017
  • Int'l Joint Research